Mitochondrion: A new molecular target and potential treatment strategies against trichothecenes

Trichothecenes are a large family of chemically related mycotoxins produced by various species of Fusarium, which is the most economically important fungal strains. Trichothecenes have most often been associated with acute and chronic toxicoses in human and livestock. Trichothecenes are linked with human diseases like alimentary toxic aleukia and Kashin-Beck disease, and also with Fusarium head blight in plants. At molecular level, the mitochondrial toxicities induced by trichothecenes have been investigated, yet no efforts are made to summarize these information. The present review provides the most recent knowledge on the mitochondrion as a new molecular target of trichothecenes based on findings that trichothecenes can cross the mitochondrial membranes and be absorbed by mitochondrion. Here, we discriminate the ROS production site in trichothecene-treated cells, and discuss the mitochondrion-dependent apoptosis and various mitochondrial toxicities induced by trichothecenes. Some mitochondrion-associated miRNAs and potential treatment strategies against trichothecenes are included, and questions not interpreted clearly and future perspective are recommended. Key findings and conclusions: Recent investigations support that mitochondrion is new molecular target of trichothecenes and should be emphasized. Namely, mitochondrion is the main site of ROS generation in trichothecene-treated cells. Trichothecenes induce collapse of mitochondrial membrane potential, and apoptosis by mitochondrial pathway. Trichothecenes inhibit mitochondrial biogenesis and respiration, ATP generation, and mitochondrial transcription and translation. Trichothecenes inhibit activity of mitochondrial electron transport chain (ETC) and change expression of ETC subunits. Trichothecenes change the expression of numbers of miRNAs and specific mitochondria-associated miRNAs which may be involved in mitochondria-dependent toxicity.